Causality of genetically determined serum metabolites on lower back pain or/and sciatica: a comprehensive Mendelian randomized study.

Background: There is an urgent need to confirm biomarkers reflecting the pathogenesis and targeted drugs of lower back pain or/and sciatica in clinical practice. This study aimed to conduct a two sample bidirectional Mendelian randomization (MR) analysis to explore the causal link between 486 serum metabolites and lower back pain or/and sciatica. Methods: All data come from two public shared databases of European ancestry and single nucleotide polymorphisms (SNPs) for lower back pain or/and sciatica acted as instrumental variables. The traditional inverse variance weighting (IVW) method, weighted-median method, MR-Egger methodand other methods were used to estimate causality. The horizontal pleiotropy, heterogeneities were also verified through the MR-Egger intercept test, Cochran's Q test, MR-PRESSO test and the leave-one-out sensitivity analysis. Reverse MR analysis was employed to evaluate the direct impact of metabolites on lower back pain or/and sciatica. Additionally, we conducted the colocalization analysis to reflect the causality deeply. Furthermore, metabolic pathway analysis was performed. Results: 28 metabolites (18 known metabolites, 1 identified metabolites and 9 unknown metabolites) relevant to the risk of sciatica or/and lower back pain after using genetic variants as probes at PIVW < 0.05 were identifed. Among them, 8 serum metabolites decreased risk of sciatica or/and lower back pain significantly (P < 0.05), and 14 serum metabolites increased risk of sciatica or/and lower back pain significantly (P < 0.05). No reverse causal association was found between 28 metabolites and sciatica or/and lower back pain. Colocalization analysis results showed that the associations between sciatica or/and lower back pain and the 28 identified metabolites were not due to shared causal variant sites. Moreover, pathway enrichment analysis identifed 11 signifcant metabolic pathways, which are mainly involved in the pathological mechanism of sciatica or/and lower back pain (P < 0.05). There was no horizontal pleiotropy or heterogeneity in the other analyses. Conclusion: Our analyses provided robust evidence of causal associations between blood metabolites on sciatica or/and lower back pain. However, the underlying mechanisms remain to be further investigated.

Distal tibial tubercle osteotomy can lessen change in patellar height post medial opening wedge high tibial osteotomy? A systematic review and meta-analysis.

OBJECTIVE: Medial opening wedge high tibial osteotomy (MOWHTO) is a mainstream surgical method for treating early medial compartment knee osteoarthritis. Undesirable sequelae such as patella infera may happen following tuberosity osteotomy. We conducted this systematic review and meta-analysis to compare the change in patellar position after proximal tibial tubercle osteotomy (PTO) versus distal tibial tubercle osteotomy (DTO) intervention. METHODS: The 11 studies were acquired from PubMed, Medline, Embase and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences, odds ratios and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Eleven observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The pooled results of postoperative patellar height (Caton-Deschamps index and Blackburne-Peel index) and postoperative complications showed that the differences were statistically significant between PTO and DTO interventions. Patellar index ratios decreased significantly in the PTO groups, and 12 (9.2%) complications under DTO surgery and 2 (1.6%) complications under PTO surgery were reported. The differences of postoperative posterior tibial slope (angle) was not statistically significant, but postoperative posterior tibial slope of both groups increased. Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. CONCLUSIONS: DTO in MOWHTO maintained the postoperative patellar height, and clinically, for patients with serious patellofemoral osteoarthritis, DTO can be preferred. Postoperative complications are easily preventable with caution. In view of the heterogeneity and small sample size, whether these conclusions are applicable should be further determined in future studies.

mRNA and long non-coding RNA expression profiles of rotator cuff tear patients reveal inflammatory features in long head of biceps tendon.

BACKGROUND: This study aimed to identify the differentially expressed mRNAs and lncRNAs in inflammatory long head of biceps tendon (LHBT) of rotator cuff tear (RCT) patients and further explore the function and potential targets of differentially expressed lncRNAs in biceps tendon pathology. METHODS: Human gene expression microarray was made between 3 inflammatory LHBT samples and 3 normal LHBT samples from RCT patients. GO analysis and KEGG pathway analysis were performed to annotate the function of differentially expressed mRNAs. The real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was admitted to verify their expression. LncRNA-mRNA co-expression network, cis-acting element, trans-acting element and transcription factor (TF) regulation analysis were constructed to predict the potential molecular regulatory mechanisms and targets for LHB tendinitis. RESULTS: 103 differentially expressed lncRNAs and mRNAs, of which 75 were up-regulated and 28 were down-regulated, were detected to be differentially expressed in LHBT. The expressions of 4 most differentially expressed lncRNAs (A2MP1, LOC100996671, COL6A4P, lnc-LRCH1-5) were confirmed by qRT-PCR. GO functional analysis indicated that related lncRNAs and mRNAs were involved in the biological processes of regulation of innate immune response, neutrophil chemotaxis, interleukin-1 cell response and others. KEGG pathway analysis indicated that related lncRNAs and mRNAs were involved in MAPK signaling pathway, NF-kappa B signaling pathway, cAMP signaling pathway and others. TF regulation analysis revealed that COL6A4P2, A2MP1 and LOC100996671 target NFKB2. CONCLUSIONS: LlncRNA-COL6A4P2, A2MP1 and LOC100996671 may regulate the inflammation of LHBT in RCT patients through NFKB2/NF-kappa B signaling pathway, and preliminarily revealed the pathological molecular mechanism of tendinitis of LHBT.

[Progress in research and development of Xanthoceras sorbifolia].

Xanthoceras sorbifolia, an excellent oil-rich woody species, has high comprehensive economic value in edible, medicinal, and ornamental fields. The chemical composition, pharmacological effect, and quality control of X. sorbifolia were introduced, and its development and application were reviewed in this study. As revealed by the previous research, the main chemical constituents of X. sorbifolia were triterpenoids, flavonoids, fatty acids, phenylpropanoids, steroids, phenolic acids, organic acids, etc. It possesses pharmacological effects, such as neuroprotection, bacteriostasis, anti-oxidation, anti-tumor, anti-inflammation, analgesia, anti-HIV, and anti-coagulation. X. sorbifolia is widely applied in medical, food, chemical industry, and other fields, and deserves in-depth research and development.

Was femoral nerve block effective for pain control of medial opening-wedge high tibial osteotomy?: A single blinded randomized controlled study.

BACKGROUND AND PURPOSE: Medial compartment femoro-tibial osteoarthritis (OA) is a common disease and opening-wedge high tibial osteotomy (OWHTO) is the common surgical procedure carried out for these patients. While most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the pain control effect of femoral nerve block (FNB) for OWHTO patients. METHODS: In this prospective, single-center, randomized controlled trial (RCT) study, 41 patients were operated on by OWHTO for OA during 2017 to 2018. Twenty of them (group A) accepted epidural anesthesia with FNB and 21 patients (group B) only had their single epidural anesthesia. All blocks were successful and all the 41 patients recruited were included in the analysis and there was no loss to follow-up or withdrawal. Systematic records of visual analog scores (VAS), quadriceps strength, mean number of times of patient-controlled intravenous analgesia (PCIA), using of additional opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), and complications were done after hospitalization. The Student t test and Chi-Squared test was used and all P values ≤.05 were considered statistically significant. RESULTS: VAS scores at rest (3.48 ±â€Š1.0 vs 4.68 ±â€Š1.1) and on movemment (4.51 ±â€Š0.6 vs 4.97 ±â€Š0.8) decreased more in group A than group B with significance at follow-up of 12 hours. The quadriceps strength, consumption of additional opioids or NSAID injections and mean number of times that the patients pushed the PCIA button didnot differ significantly within each group. CONCLUSION: This RCT study shows that FNB in patients undergoing OWHTO for unicompartmental osteoarthritis of the knee could result in significant reduction in VAS scores at 12 hours postoperatively.Research registry, Researchregistry4792. Registered April 7, 2019 - Retrospectively registered, http://www.researchregistry.com.

Vitamin D3 protects articular cartilage by inhibiting the Wnt/ß-catenin signaling pathway.

Low expression levels of 25-hydroxyvitamin D (vitamin D3) in the blood have been reported to be associated with the progression of osteoarthritis; however, the mechanisms by which this occurs remain unclear. The present study aimed to determine the effects of vitamin D3 on chondrocytes. MTT assays were used to determine whether vitamin D3 affects chondrocytes viability. Primary chondrocytes were treated with control culture medium, vitamin D3, tumor necrosis factor (TNF)-α, TNF-α + PNU-74654 [Wingless-related integration site (Wnt)/ß-catenin signaling pathway inhibitor] or TNF-α + vitamin D3. Reverse transcription-quantitative PCR and western blotting were utilized to measure the gene and protein expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-3 and MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, Wnt-3a and nuclear ß-catenin. The results demonstrated that TNF-α reduced the expression levels of aggrecan and collagen II, and increased the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5. Furthermore, vitamin D3 and PNU-74654 were observed to partially attenuate the effects induced by TNF-α. Moreover, similar findings were reported following co-treatment with vitamin D3 and TNF-α. Western blotting data revealed that TNF-α increased Wnt-3a and ß-catenin protein levels in chondrocytes, while Vitamin D3 and PNU-74654 decreased the expression levels of Wnt-3a and nuclear ß-catenin. In conclusion, the findings of the present study provided evidence to suggest that vitamin D3 may prevent articular cartilage degeneration and osteoarthritic disease progression by inhibiting the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 through suppressing the Wnt/ß-catenin signaling pathway. These results suggested that vitamin D3 may be of therapeutic value for the prevention and treatment of osteoarthritis.

Opening-Wedge High Tibial Osteotomy Using Autograft versus Allograft: A Systematic Review and Meta-analysis.

Bone grafting is a good alternative for filling the inevitable void that is created following opening-wedge high tibial osteotomy (OWHTO). This systematic review and meta-analysis evaluated whether bone grafting is necessary for OWHTO and the successful outcomes of OWHTO using either autograft (AU) or allograft (AL). All analyzed studies were acquired from PubMed, Medline, Embase, CNKI, Google Scholar, and Cochrane Library. Data were independently extracted by two coauthors and were analyzed using RevMan5.3. Mean differences, odds ratios, and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess the risk of bias. In total, 10 studies were assessed including three randomized controlled trials and seven observational studies. The methodological quality of the trials ranged from low to high. The overall estimate demonstrated that the difference between OWHTO using AU and AL groups and OWHTO using no filling group was not statistically significant for the loss of correction, and complications, but OWHTO using no filling group statistically showed better knee society score. Pooled results of reoperations, lateral cortex breaches, complications, and clinical function assessments showed no significant difference between AU and AL materials. Using AL statistically reduced the operative time compared with using AU. OWHTO with or without bone graft does not affect postoperative complications. No loss of correction was observed due to the lack of bone grafting. In addition, OWHTO without bone graft performs better for postoperative clinical function assessment. Complications and clinical results of medial OWHTO were similar using AL and AU and neither reported a median loss of correction of following OWHTO. Compared with using AU, using AL avoids harvest site complications and reduces operative time. To sum up, OWHTO without any bone graft is recommended for medial unicompartmental osteoarthritis of the knee. Further large-sample, multicenter, high-quality, randomized controlled trials are warranted to verify the outcomes of this meta-analysis.

The Value of the Inferior Vena Cava Area Distensibility Index and its Diameter Ratio for Predicting Fluid Responsiveness in Mechanically Ventilated Patients.

INTRODUCTION: It is necessary to evaluate fluid responsiveness before fluid resuscitation. We evaluated the value of inferior vena cava (IVC) area respiratory variation and the IVC diameter ratio (IVC DR) for predicting fluid responsiveness in mechanically ventilated patients. METHODS: A prospective observational study was performed in the intensive care unit between December 2017 and March 2018. Mechanically ventilated patients were enrolled and received ultrasound monitoring. IVC diameter distensibility index from the subxiphoid area (IVC-sx DDI), IVC diameter distensibility index from the right midaxillary line (IVC-rm DDI), IVC area distensibility index (IVC ADI), and IVC DR in cross-section were calculated by ultrasound monitoring IVC parameters. The enrolled patients were classified as nonresponders group and responders group according to whether the cardiac output increased by >10% after passive leg raising. RESULTS: Data from 67 mechanically ventilated patients were analyzed. 55.2% of patients had positive fluid responsiveness. The area of receiver operating characteristic curves evaluating the ability of the IVC-sx DDI, IVC-rm DDI, IVC ADI, and IVC DR to predict the fluid responsiveness were 0.702, 0.686, 0.749, and 0.829, respectively. IVC DR level of 1.43 was predictive of positive fluid responsiveness with 90.0% specificity and 67.6% sensitivity. IVC ADI level of 10.2% was predictive of positive fluid responsiveness with 40.0% specificity and 97.3% sensitivity. CONCLUSIONS: IVC ADI and its diameter ratio in cross-section had more value than IVC diameter distensibility index for predicting fluid responsiveness in mechanically ventilated patients.

Comparison of arthroscopic suture-bridge technique and double-row technique for treating rotator cuff tears: A PRISMA meta-analysis.

BACKGROUND: Rotator cuff tear is a common shoulder disorder in the elderly. Either arthroscopic double-row (DR) or suture-bridge (SB) technique for rotator cuff tear patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic SB versus DR intervention. METHODS: The 7 studies were acquired from PubMed, Medline, Embase, CNKI, Google, and Cochrane Library. The data were extracted by 2 of the co-authors independently and were analyzed by RevMan5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa scale were used to assess risk of bias. RESULTS: Seven studies including 1 randomized controlled trial and 6 observational studies were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of American Shoulder and Elbow Surgeons score, Constant score, visual analog scale score, and range of motion showed that the differences were not statistically significant between the 2 interventions. The difference of University of California at Los Angeles (UCLA) score was statistically significant between SB and DR intervention, and SB treatment was more effective (MD = -0.95, 95% CI = -1.70 to -0.20, P = .01). The difference of re-tear rate was statistically significant and SB treatment achieved better result than DR treatment (OR = 0.31, 95% CI = 0.15-0.64, P = .001). Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. CONCLUSIONS: Both arthroscopic SB and DR interventions had benefits in rotator cuff tear. SB treatment was more effective in UCLA score and had lower re-tear rate than DR treatment. The arthroscopic SB technique is recommended as the optical choice for rotator cuff tear.

Is arthroscopic repair superior to biceps tenotomy and tenodesis for type II SLAP lesions? A meta-analysis of RCTs and observational studies.

OBJECTIVE: Labral repair and biceps tenotomy and tenodesis are routine operations for type II superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their superiority is lacking. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic repair versus biceps tenotomy and tenodesis intervention. METHODS: The eight studies were acquired from PubMed, Medline, Embase, CNKI, and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan 5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Eight studies including two randomized controlled trials (RCTs) and six observational studies were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of UCLA score, SST score, and complications showed that the differences were not statistically significant between the two interventions. The difference of ASES score and satisfaction rate was statistically significant between arthroscopic repair and biceps tenotomy and tenodesis intervention, and arthroscopic biceps tenotomy and tenodesis treatment was more effective. Sensitivity analysis proved the stability of the pooled results, and there were too less included articles to verify the publication bias. CONCLUSIONS: Both arthroscopic repair and biceps tenotomy and tenodesis interventions had benefits in type II SLAP lesions. Arthroscopic biceps tenotomy and tenodesis treatment provides better clinical outcome in ASES score and satisfaction rate and comparable complications compared with arthroscopic repair treatment. In view of the heterogeneity and confounding factors, whether these conclusions are applicable should be further determined in future studies.

Respiratory variation in peripheral arterial blood flow peak velocity to predict fluid responsiveness in mechanically ventilated patients: a systematic review and meta-analysis.

BACKGROUND: Fluid overloading is detrimental to organ function and results in a poor prognosis. It is necessary to evaluate fluid responsiveness before fluid loading. We performed a systematic meta-analysis to evaluate the diagnostic value of the respiratory variation in peripheral arterial blood flow peak velocity (△Vpeak PA) in predicting fluid responsiveness in mechanically ventilated patients. METHODS: PubMed, Embase and The Cochrane Library databases were searched for studies that used △Vpeak PA to predict fluid responsiveness in mechanically ventilated patients. We calculated the pooled values of sensitivity, specificity and the area of the summary receiver operating characteristic curve by Meta-Disc 14.0 software. RESULTS: Nine studies with a total of 402 patients were included. Two low quality studies were deleted in further analysis. Moreover, because of different locations of peripheral artery, the rest included studies were divided into brachial site group and carotid site group for meta-analysis individually. The pooled sensitivity, specificity and area under curve were 0.85 (95% confidence interval (CI) 0.77-0.92), 0.86 (95% CI 0.77-0.92) and 0.9268 in carotid site group. The pooled sensitivity, specificity and area under curve were 0.72 (95% CI 0.60-0.81), 0.85 (95% CI 0.74-0.93) and 0.8587 in brachial site group. CONCLUSIONS: △Vpeak of carotid and brachial artery had a diagnostic value in predicting fluid responsiveness respectively. Moreover, △Vpeak of carotid artery had more value than brachial artery in predicting fluid responsiveness. However, there was some clinical heterogeneity; therefore, further studies are needed to confirm diagnostic accuracy.

Bioinformatics analysis of differentially expressed genes in rotator cuff tear patients using microarray data.

BACKGROUND: Rotator cuff tear (RCT) is a common shoulder disorder in the elderly. Muscle atrophy, denervation and fatty infiltration exert secondary injuries on torn rotator cuff muscles. It has been reported that satellite cells (SCs) play roles in pathogenic process and regenerative capacity of human RCT via regulating of target genes. This study aims to complement the differentially expressed genes (DEGs) of SCs that regulated between the torn supraspinatus (SSP) samples and intact subscapularis (SSC) samples, identify their functions and molecular pathways. METHODS: The gene expression profile GSE93661 was downloaded and bioinformatics analysis was made. RESULTS: Five hundred fifty one DEGs totally were identified. Among them, 272 DEGs were overexpressed, and the remaining 279 DEGs were underexpressed. Gene ontology (GO) and pathway enrichment analysis of target genes were performed. We furthermore identified some relevant core genes using gene-gene interaction network analysis such as GNG13, GCG, NOTCH1, BCL2, NMUR2, PMCH, FFAR1, AVPR2, GNA14, and KALRN, that may contribute to the understanding of the molecular mechanisms of secondary injuries in RCT. We also discovered that GNG13/calcium signaling pathway is highly correlated with the denervation atrophy pathological process of RCT. CONCLUSION: These genes and pathways provide a new perspective for revealing the underlying pathological mechanisms and therapy strategy of RCT.

Exploring the Key Genes and Pathways of Osteoarthritis in Knee Cartilage in a Rat Model Using Gene Expression Profiling.

PURPOSE: To compare differentially expressed genes (DEGs) mediating osteoarthritis (OA) in knee cartilage and in normal knee cartilage in a rat model of OA and to identify their impact on molecular pathways associated with OA. MATERIALS AND METHODS: A gene expression profile was downloaded from the Gene Expression Omnibus database. Analysis of DEGs was carried out using GEO2R. Enrichment analyses were performed on the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway using the Search Tool for the Retrieval of Interacting Genes database (http://www.string-db.org/). Subsequently, the regulatory interaction network of OA-associated genes was visualized using Cytoscape software (version 3.4.0; www.cytoscape.org). RESULTS: In the gene expression profile GSE103416, a total of 99 DEGs were identified. Among them, 76 DEGs (76.77%) were overexpressed, and the remaining 23 DEGs (23.23%) were underexpressed. GO and pathway enrichment analyses of target genes were performed. Using gene-gene interaction network analysis, relevant core genes, including MET, UBB, GNAI3, and GNA13, were shown to hold a potential relationship with the development of OA in cartilage. Using quantitative real-time PCR, the Gna13/cGMP-PKG signaling pathway was identified as a potential research target for therapy and for further understanding the development of OA. CONCLUSION: The results of the present study provide a comprehensive understanding of the roles of DEGs in knee cartilage in relation to the development of OA.

Exploring the key genes and pathways of side population cells in human osteosarcoma using gene expression array analysis.

BACKGROUND: Human osteosarcoma (OS) is one of the most common primary bone sarcoma, because of early metastasis and few treatment strategies. It has been reported that the tumorigenicity and self-renewal capacity of side population (SP) cells play roles in human OS via regulating of target genes. This study aims to complement the differentially expressed genes (DEGs) that regulated between the SP cells and the non-SP cells from primary human OS and identify their functions and molecular pathways associated with OS. METHODS: The gene expression profile GSE63390 was downloaded, and bioinformatics analysis was made. RESULTS: One hundred forty-one DEGs totally were identified. Among them, 72 DEGs (51.06%) were overexpressed, and the remaining 69 DEGs (48.94%) were underexpressed. Gene ontology (GO) and pathway enrichment analysis of target genes were performed. We furthermore identified some relevant core genes using gene-gene interaction network analysis such as EIF4E, FAU, HSPD1, IL-6, and KISS1, which may have a relationship with the development process of OS. We also discovered that EIF4E/mTOR signaling pathway could be a potential research target for therapy and tumorigenesis of OS. CONCLUSION: This analysis provides a comprehensive understanding of the roles of DEGs coming from SP cells in the development of OS. However, these predictions need further experimental validation in future studies.

Short-term Follow-up of Antibiotic-loaded Articulating Cement Spacers in Two-stage Revision of Infected Total Knee Arthroplasty: A Case Series.

OBJECTIVE: Infection of total knee arthroplasty (TKA) is a rare but devastating complication. Two-stage revision is an effective treatment for late infected TKA. This study aimed to assess the short-term results of two-stage revision using articulating antibiotic-loaded spacers. METHODS: Twenty-five patients (10 men and 15 women) were diagnosed with late infections after TKA and treated with two-stage revision from April 2006 to August 2010; 19 of these patients had TKA for osteoarthritis and 6 for rheumatoid arthritis. Median age was 64.9 (range, 56-83) years. In the first-stage surgery, the prosthesis and all bone cement was removed. After thorough debridement, bone cement with vancomycin and tobramycin was put into a die cavity and made into temporary femoral and tibial spacers, respectively. In the cases of good knee range of motion, the temporary spacers were affixed to the bone surface using the same antibiotic bone cement. In the second surgery, gentamycin Refobacin Bone Cement with vancomycin was used to fix the prosthesis. After two-stage revision, patients were followed up clinically and radiologically at 1, 3, and 6 months, and then annually. Knee Society Score (KSS), knee function score, knee pain score, and knee range of motion (ROM) were assessed. RESULTS: Among the group, all spacers were easily removed, and bone defect degree showed no obvious change compared with pre-implant, 24 (96%) patients had been debrided once, and 1 patient had been debrided twice before reimplant prosthesis. Mean follow-up was 64.2 (range, 52-89) months. There was no infection recurrence at final follow-up. Compared with preoperative data, the KSS (66 [59, 71], 83 [80, 88] vs 46 [43, 57], P < 0.01), knee function score (43 [42, 49], 78 [73, 82] vs 32 [25, 37], P < 0.01), knee pain score (34 [33, 37], 42 [40, 45] vs 18 [16, 23], P < 0.01), and knee ROM (92° [86°, 96°], 94° [90°, 98°] vs 78° [67°, 86°], P < 0.01) were all improved during follow-up and at final visit. Three patients experienced complications in the interval period: one case had knee dislocation, one had knee instability, and one had a chip in the femoral component of the spacer. CONCLUSION: Using articulating antibiotic-loaded spacers showed benefits for treating infected TKA in selected patients. No infection recurrence was observed during follow-up.

Modulation of mitogen­activated protein kinase attenuates sepsis­induced acute lung injury in acute respiratory distress syndrome rats.

Sepsis is the most important predisposing cause inducing acute respiratory distress syndrome (ARDS); however, the mechanism of sepsis leading to the development of ARDS remains to be elucidated. Suppression of the mitogen­activated protein kinase (MAPK) signal by blocking the phosphorylation of Jun N­terminal kinase (JNK) and p38 in lung tissues could alleviate acute lung injury induced by sepsis. MAPK signaling may have a crucial role in development of the sepsis­induced acute lung injury. The specific inhibitors of JNK and p38 MAPK, SP600125 and SB203580, were administrated by intragastric injection 4 h before induction of ARDS after cecal ligation and puncture (CLP). Rats were sacrificed at 1, 6 or 24 h after CLP challenge. The histological evaluation, lung water content, and biochemical analysis were performed. The results revealed that the JNK and p38 MAPK inhibitor improved lung permeability, attenuated system inflammation, further alleviated the lung injury induced by sepsis. In conclusion, JNK and p38 MAPK signaling are essential for the development of ARDS following sepsis. Further studies are needed to illuminate the detailed mechanisms of JNK and p38 MAPK signaling in sepsis­induced ARDS.

Effects of early rehabilitation therapy on patients with mechanical ventilation.

BACKGROUND: For patients in intensive care unit (ICU), mechanical ventilation is an effective treatment to survive from acute illness and improve survival rates. However, long periods of bed rest and restricted physical activity can result in side effects. This study aimed to investigate the feasibility of early rehabilitation therapy in patients with mechanical ventilation. METHODS: A randomized controlled trial was carried out. Sixty patients, with tracheal intubation or tracheostomy more than 48 hours and less than 72 hours, were admitted to the ICU of the Affiliated Hospital of Medical College, Qingdao University, from May 2010 to May 2012. These patients were randomly divided into a rehabilitation group and a control group. In the rehabilitation group, rehabilitation therapy was performed twice daily, and the training time and intensity were adjusted according to the condition of the patients. Early rehabilitation therapy included heading up actively, transferring from the supine position to sitting position, sitting at the edge of the bed, sitting in chair, transferring from sitting to standing, and ambulating bedside. The patient's body mass index, days to first out of bed, duration of mechanical ventilation, length of ICU stay, APACHE II score, highest FiO2, lowest PaO2/FiO2 and hospital mortality of patients were all compared between the rehabilitation group and the control group. The differences between the two groups were compared using Student's t test. RESULTS: There was no significant difference in body mass index, APACHE II score, highest FiO2, lowest PaO2/FiO2 and hospital mortality between the rehabilitation group and the control group (P>0.05). Patients in the rehabilitation group had shorter days to first out of bed (3.8±1.2 d vs. 7.3±2.8 d; P=0.00), duration of mechanical ventilation (5.6±2.1 d vs. 12.7±4.1 d; P=0.005) and length of ICU stay (12.7±4.1 d vs. 15.2±4.5 d; P=0.01) compared with the control group. CONCLUSION: Early rehabilitation therapy was feasible and effective in improving the outcomes of patients with mechanical ventilation.

Recombinant adeno-associated virus serotype 1-vascular endothelial growth factor promotes neurogenesis and neuromigration in the subventricular zone and rescues neuronal function in ischemic rats.

OBJECTIVE: Vascular endothelial growth factor (VEGF) enhances neurogenesis in ischemic brains. However, in most circumstances, endogenous VEGF expression is limited and insufficient to prevent brain damage. We transferred the VEGF gene into brain tissue with recombinant adeno-associated virus serotype 1 (rAAV1) vectors and determined the effect of VEGF expression on neurogenesis and recovery of neurological function after brain ischemia. METHODS: Two groups (n = 32) of Sprague Dawley rats received intraventricular injection of AAV1-VEGF or AAV1-lacZ. Twenty-one days after gene transfer, rats underwent transient middle cerebral artery occlusion, and neurological severity score was measured 1, 2, 3, 7, 14, and 21 days later. Immunostaining was used to identify the quantity and distribution of VEGF expression. Double-immunofluorescence for doublecortin and bromodeoxyuridine or neuronal nuclei was performed to detect neurogenesis and the migration of neural progenitor cells. RESULTS: VEGF expression reduced the size of cerebral infarction and improved neurological function. It also enhanced the proliferation of neural progenitor cells in the subventricular zone and promoted their migration to the ischemic lesion. Neural precursors in the subgranular zone of the dentate gyrus were also increased; however, most of these cells did not move to the ischemic lesion and integrated with their region of origin. CONCLUSION: rAAV1-mediated expression of VEGF in the rat brain reduces the size of the infarcted lesion and promotes recovery of neurological function, likely by enhancing neurogenesis in the subventricular zone and promoting neural precursor migration to brain tissue around the core of the ischemic lesion.